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Published on: February 14, 2020
The cross-link breaker, N-phenacylthiazolium bromide prevents vascular advanced glycation end-product accumulation
M E Cooper1, V Thallas, J Forbes
1Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, West Heidelberg, Australia.
Aims/Hypothesis:
Advanced glycation is postulated to have a pivotal role in mediating diabetic vascular complications. The emergence of thiazolium compounds such as N-phenacylthiazolium bromide which cleave preformed advanced glycation end products (AGEs) has allowed us to explore the effects of these agents on the vascular AGE accumulation and hypertrophy associated with diabetes.
Methods:
Control and streptozotocin diabetic rats were selected at random for no treatment or treatment with N-phenacylthiazolium bromide (10 mg/kg intraperitoneally) and followed for 3 weeks. In a separate study, intervention with N-phenacylthiazolium bromide was delayed until after 3 weeks of diabetes and then given for 3 weeks (total of 6 weeks).
Results:
Diabetes was associated with increased mesenteric vascular advanced glycation end products, as assessed by radioimmunoassay and immunohistochemistry. This increase in vascular AGE accumulation was prevented by N-phenacylthiazolium bromide treatment. Diabetes-associated mesenteric vascular hypertrophy was attenuated by treatment with N-phenacylthiazolium bromide only if given from the time of induction of diabetes.
Conclusion/Interpretation:
Cross-link breakers seem to be effective in preventing or reversing accumulation of advanced glycation end-products in blood vessels and have the potential to play a part in the treatment of diabetic vascular complications.
Insights
N-phenacylthiazolium bromide, a cross-link breaker, prevents advanced glycation end-product accumulation in diabetic blood vessels. Early treatment with this compound also attenuates vascular hypertrophy, offering potential for diabetic complication management.
Area of Science:
- Vascular Biology
- Diabetic Complications
- Pharmacology
Background:
- Advanced glycation end products (AGEs) are implicated in diabetic vascular complications.
- Thiazolium compounds, like N-phenacylthiazolium bromide, can cleave preformed AGEs.
Purpose of the Study:
- To investigate the effect of N-phenacylthiazolium bromide on vascular AGE accumulation and hypertrophy in diabetic rats.
- To explore the therapeutic potential of AGE cross-link breakers in managing diabetic vascular disease.
Main Methods:
- Control and streptozotocin-induced diabetic rats were treated with N-phenacylthiazolium bromide (10 mg/kg) for 3 or 6 weeks.
- Vascular AGE accumulation was assessed using radioimmunoassay and immunohistochemistry.
- Mesenteric vascular hypertrophy was measured to evaluate treatment efficacy.
Main Results:
- Diabetes significantly increased mesenteric vascular AGEs.
- N-phenacylthiazolium bromide treatment prevented AGE accumulation.
- Vascular hypertrophy was attenuated by early N-phenacylthiazolium bromide intervention.
Conclusions:
- AGE cross-link breakers are effective in preventing and potentially reversing vascular AGE accumulation.
- Early intervention with N-phenacylthiazolium bromide shows promise in mitigating diabetic vascular hypertrophy.
- These findings suggest a potential role for AGE cross-link breakers in treating diabetic vascular complications.
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